Three doses of sodium monoiodoacetate (MIA) were used to induce degenerative changes in articular cartilage in middle carpal joints of horses. Twelve young (2- to 5-year-old) horses, free of lameness, were randomly allotted to 3 groups. One middle carpal joint of each horse was injected with 0.9% NaCl solution (control joint). The contralateral middle carpal joint was injected with 0.09 mg of MIA/kg of body weight (group 1); 0.12 mg(kg (group 2); or 0.16 mg(kg (group 3). After MIA administration, horses were allowed ad libitum exercise in a 2-acre paddock for 12 weeks. At the end of the study, gross and microscopic tissue changes were evaluated and biochemical analyses of articular cartilage were done. Grossly, diffuse partial-thickness articular cartilage lesions were observed in group-2 (n = 2) and group-3 (n = 4) horses, but not in group-1 horses. Articular cartilage uronic acid content was significantly (P < 0.03) decreased in all MIA-injected joints, compared with controls. Articular cartilage matrix staining with safranin-O was decreased in 3 of 4 MIA-injected joints of group-1 horses and in all MIA-injected joints of group-2 and group-3 horses, compared with controls (P < 0.06). Microscopic degenerative changes in articular cartilage were not significantly different between MIA-injected and control joints in group-1 horses, but were increased (P < 0.06) in all MIA-injected joints of group-2 and group-3 horses, compared with controls. Qualitatively, decreased matrix staining and degenerative changes were more severe in group-3 horses. On the basis of articular cartilage gross and microscopic changes, as well as biochemical changes, 0.12 mg of MIA/kg injected intra-articularly was determined to induce moderate degrees of articular cartilage degeneration. This model of chemically induced articular cartilage injury could be useful for evaluating treatment effects of anti-arthritic drugs in horses.

Because articular chondrocytes are a target for drugs that can influence the integrity of cartilage, we investigated the effects of 3 antiarthritic drugs, glycosaminoglycan polysulfate, diclofenac-Na, and S-adenosylmethionine sulfate p-toluenesulfonate on total protein, fibronectin, and DNA synthesis, as well as on extradomain-A fibronectin and keratan sulfate content. Glycosaminoglycan polysulfate stimulated dose-dependent incorporation of [35S]methionine into protein and fibronectin, whereas incorporation of [3H]thymidine into DNA was unaffected. Total fibronectin, extradomain-A fibronectin, and keratan sulfate content were high in chondrocyte cultures treated with glycosaminoglycan polysulfate. In contrast, fibronectin and DNA synthesis, as well as extradomain-A fibronectin and keratan sulfate content were unaffected by diclofenac-Na. S-adenosylmethionine decreased dose-dependently the synthesis of fibronectin, as well as the content of fibronectin and keratan sulfate. At the highest concentration of S-adenosylmethionine tested, findings suggest that cell viability was impaired as assessed by the release of lactate dehydrogenase into the media.

A circular (5.5 mm diameter) full-thickness cartilage defect was created on the medial ridge of the talus in 12 skeletally mature dogs. In 6 dogs, the articular surface of the lesion was repaired, using an osteochondral graft obtained from the ipsilateral manus. The graft (digit I, first phalanx, distal articular surface and diaphysis) was contoured to obtain a press fit in the drilled talar recipient site. In 6 dogs, the lesion was not treated and healed by fibrous tissue replacement. Functional assessment (lameness, hock range of motion, joint stability, joint crepitus, and mid-femoral muscle circumference) was completed before surgery and at postoperative weeks 2 through 20. Radiographic assessment (periarticular soft tissue width, joint space width, osteophyte formation, and graft incorporation) was completed before surgery and at postoperative weeks 0, 6, 12, and 20. To facilitate histologic assessment, tissues were stained with toluidine blue and H&E. Histologic assessment of the articular surface on the surgically treated talus, ipsilateral tibia, and contralateral talus was completed, using a modification of the Mankin grading system. Subchondral bone was examined to assess graft viability and incorporation. Analysis of the ordinal data was completed, using a Mann-Whitney rank sum test. All dogs were fully weight bearing by postoperative week 7. Dogs without grafts had significantly (P = 0.036) better clinical function at postoperative week 6. Significant difference in functional assessment was not evident at postoperative week 20. Immediate postoperative radiographic assessment revealed significant (P = 0.005) difference between nongrafted and grafted groups. Significant difference was not observed at postoperative week 6, 12, or 20. All grafts appeared radiographically incorporated by postoperative week 12. All grafts restored joint surface congruity, whereas 3 of 6 nongrafted lesions had poor articular congruity. Of 6 grafts, 4 partially retained normal hyaline cartilage, resulting in significantly (P = 0.014) lower Mankin grades. Significant histologic differences between groups were not apparent when the apposing tibia and control talus were examined. Talar reconstruction by use of a phalangeal osteochondral graft is a viable surgical procedure. These data indicate that normal articular and subchondral architecture are more closely approximated by osteochondral reconstruction than by fibrous tissue repair.

Using biodegradable pins, sternal cartilage autografts were fixed into osteochondral defects of the distal radial carpal bone in ten 2 to 3-year-old horses. The defects measured 1 cm2 at the surface and were 4 mm deep. Control osteochondral defects of contralateral carpi were not grafted. After confinement for 7 weeks, horses were walked 1 hour daily on a walker for an additional 9 weeks. Horses were euthanatized at 16 weeks. Half of the repair tissue was processed for histologic and histochemical (H&E and safranin-O fast green) examinations. The other half was used for the following biochemical analyses: type-I and type-II collagen contents, total glycosaminoglycan content, and galactosamine-to-glucosamine ratio. On histologic examination, the repair tissue in the grafted defects consisted of hyaline-like cartilage. Repair tissue in the nongrafted defects consisted of fibrocartilaginous tissue, with fibrous tissue in surface layers. On biochemical analysis, repair tissue of grafted defects was composed predominantly of type-II collagen; repair tissue of nongrafted defects was composed of type-I collagen. Total glycosaminoglycan content of repair tissue of grafted defects was similar to that of normal articular cartilage. Total glycosaminoglycan content of nongrafted defects was 62% of that of normal articular cartilage (P < 0.05). Repair tissue of all defects was characterized by galactosamine-to-glucosamine ratio significantly (P < 0.05) higher than that of normal articular cartilage. These results at 16 weeks after grafting indicate that sternal cartilage may potentially constitute a suitable substitute for articular cartilage in large osteochondral defects of horses.

Explant cultures were set up, using articular cartilage obtained from metatarsophalangeal joints of 11 horses. Explants from 2 horses were used to determine culture conditions appropriate for tissue viability. The cartilage explants maintained steady-state metabolism of proteoglycans during a 13-day evaluation period. The metabolic response of equine articular cartilage to incubation with recombinant human interleukin 1 (0.01 to 100 ng/ml) was studied, using cartilage obtained from the remaining 9 horses, age of which ranged from 3 months to 20 years. Interleukin 1 induced a dose-dependent release of glycosaminoglycan from the matrix during a 3-day incubation period. It also caused dose-dependent inhibition of glycosaminoglycan synthesis during a 3-hour pulse-labeling period. Explants obtained from older horses were significantly (P < 0.05) less responsive to interleukin 1, with respect to synthesis and release of glycosaminoglycan.

The effects of intra-articular administration of methylprednisolone acetate (MPA) on the healing of full-thickness osteochondral defects and on normal cartilage were evaluated in 8 horses. In group-1 horses (n = 4), a 1-cm-diameter, full-thickness defect was created bilaterally in the articular cartilage on the dorsal distal surface of the radial carpal bone. Cartilage defects were not created in group-2 horses (n = 4). One middle carpal joint was randomly selected in each horse (groups 1 and 2), and treated with an intra-articular injection of 100 mg Of MPA, once a week for 4 treatments. Injections began 1 week after surgery in group-1 horses. The contralateral middle carpal joint received intra-articular injections of an equivalent volume of 0.9% sodium chloride solution (SCS), and served as a control. Horses were evaluated for 16 weeks, then were euthanatized, and the middle carpal joints were examined and photographed. Synovial and articular cartilage specimens were obtained for histologic and histochemical evaluation. Gross morphometric evaluation of the healing defects in group-1 horses revealed that 48.6% of the defect in control joints and 0% of the defect in MPA-treated joints was resurfaced with a smooth, white tissue, histologically confirmed as fibrocartilage. This replacement tissue was a firmly attached fibrocartilage in control joints and a thin fibrous tissue in MPA-treated joints. The articular cartilage in joints treated with MPA had morphologic changes, including chondrocyte cluster formation, loss of palisading architecture, and cellular necrosis in both groups of horses. Histochemical (safranin-0) staining intensity was reduced significantly (P < 0.05) in all layers of articular cartilage in MPA-treated joints in groups 1 and 2. In the replacement tissue, intense safranin-O staining was found only in the chondrocyte clusters deep in the tissue of control joints, confirming fibrocartilage repair. Intra-articular administration of MPA in this dosing regimen thus induced degenerative changes in normal articular cartilage and resulted in histomorphologic changes in the repair of full-thickness articular osteochondral defects in horses.